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Questions on antimicrobial resistance

The critical issue of the growth in antimicrobial resistance in animal and human bacteria requires an integrated approach across all types of medicine, in line with the implementation of a "One Health" approach. ANSES plays a very active role in the fight against antimicrobial resistance, in particular by coordinating the French Surveillance Network for Antimicrobial Resistance in Pathogenic Bacteria of Animal Origin (Résapath), conducting benefit/risk assessments before marketing authorisations can be granted for antimicrobials in veterinary medicine, monitoring sales volumes in veterinary medicine, and assessing the risks associated with the use of antibiotics in animal health, as well as through its research and reference activities. Jean-Pierre Orand, Director of the French Agency for Veterinary Medicinal Products (ANMV), Jean-Yves Madec, Scientific Director in charge of Antimicrobial Resistance and Gilles Salvat, Director for Animal Health and Welfare, tell us more about the progress made in recent years to combat antimicrobial resistance.

A few weeks ago, the ANMV published the 2016 results of its annual monitoring of sales of veterinary antimicrobials. What are the main findings?

Jean-Pierre Orand: Overall exposure of animals to antimicrobials has continued to decline in recent years: in five years, it has fallen by 36.6% in all animal species, all antimicrobials combined. Exposure to antimicrobials referred to as "critical to human health" has also fallen significantly: by 81.3% for newer-generation cephalosporins, and by 74.9% for fluoroquinolones, all species combined, over the last three years. The objectives of the first EcoAntibio plan have therefore been achieved, and even greatly exceeded. These reductions confirm the positive impact of the various measures taken regarding the prudent use of antimicrobials, and also testify to the commitment of all the players in the sectors involved. concernées.

Today, you are publishing the results from Résapath's national surveillance of resistance. Do they confirm this progress?

Jean-Yves Madec: First of all, remember what Résapath does: it collects antibiogram data on pathogenic bacteria isolated from sick animals. It can therefore monitor changes in resistance to antimicrobials associated with animal infections, detect the emergence of certain antimicrobial resistance phenomena and characterise their molecular mechanisms. In 2016, the network again recorded a decrease in resistance to critical antimicrobials, including that of E. coli to third- and fourth-generation cephalosporins.

More generally, the last ten years have seen a decline or stabilisation for the vast majority of antimicrobials tested. The decrease in resistance to tetracycline in the poultry sectors, and to a lesser extent in the swine sector, is the most striking phenomenon. It should also be noted that the proportion of multi-resistant bacterial strains has fallen significantly in all species.

These results are consistent with the significant reductions in animal exposure to antimicrobials, and have also been confirmed in human medicine. However, the veterinary profession needs to remain vigilant and mobilised for this progress to be sustained.

What about colistin, which had raised questions at the end of 2015, after the first plasmid-mediated mechanism of resistance to colistin was identified?

Jean-Pierre Orand: Indeed, this discovery led to the establishment of specific management measures (such as amendments to the marketing authorisations for veterinary medicinal products containing this antibiotic) and enhanced surveillance. After having increased until 2007 and then stabilised until 2011, exposure to colistin has been falling over the past few years, with a 55.1% reduction in exposure being observed. It is a very encouraging result.

Jean-Yves Madec: The use of colistin in veterinary medicine has been the subject of numerous debates over the past few years, mainly because of the importance of this compound in human medicine in severe cases where no further therapeutic options are available. Despite the presence of these plasmid genes in the animal sector, the data on colistin collected by Résapath show that the spread of pathogenic E. coli bacteria resistant to this antimicrobial is under control, regardless of the type of animal production. It is a very significant result in epidemiological terms.

What are your recommendations to ensure that these trends continue in the years to come?

Gilles Salvat: The actions taken by farmers and veterinarians, such as limiting the use of cephalosporins in the swine sector, training modules for farmers, or the drafting of good practice guides, accompanied by the EcoAntibio 2017 plan, have helped achieve the various objectives. This approach must be maintained, by continuing to support the farmers and veterinarians, as emphasised in the EcoAntibio 2 plan (2017-2021). The decline in the use of antimicrobials necessarily requires the continued improvement of health control on farms, the development of alternatives to antimicrobials, the study of the economic impact of the recommended measures, and better knowledge of the sociological component of the reliance on antimicrobials. Sociologists, economists and biologists should work together to achieve this.

Surveillance of the risks and benefits of veterinary medicinal products: 2016 report

Through the French Agency for Veterinary Medicinal Products (ANMV), ANSES is tasked with assessing and managing risks associated with veterinary medicinal products in France. In particular, it is responsible for the continued surveillance of the risks and benefits of veterinary medicinal products, after they have been placed on the market. This helps ensure they can be used in complete safety.

Today, the Agency is publishing its 2016 activity report on surveillance of the French veterinary medicinal products market and the pharmacovigilance scheme. Since 2011, the number of reports received has continued to rise (+46%). In 2016, the ANMV recorded 4113 cases of adverse effects in animals, 51% of which were considered serious. More than 90% of these reports were sent by veterinary practitioners, while those submitted by animal owners and breeders accounted for nearly 8%.

As each year, the vast majority of the adverse effects reported in 2016 involved domestic carnivores, with around 80% of reports concerning dogs or cats. Cattle represented 9% of all reports. Other species accounted for less than 3% per species.

Pharmacovigilance also concerns suspicions of lack of efficacy, information about potential environmental risks, and information about the validity of withdrawal periods for veterinary medicinal products. Suspicions of lack of efficacy accounted for nearly 11% of all reports and other cases accounted for less than 0.4%. The total number of reports of lack of efficacy increased yet again in 2016: 406 declarations compared with 363 in 2015.

These different developments testify to greater awareness of pharmacovigilance among veterinarians and farmers, thanks in part to the communication and training measures implemented in recent years by the ANMV.